*5.3.3 Pharmacotherapy of dyslipidemia*

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

recommended, preferably in association with GLP-1 RA [53].

and Diamicron MR Controlled Evaluation) is the only one that has shown that gliclazide is CV neutral and has beneficial effects in reducing kidney disease [60]. The PROactive study (PROspective pioglitAzone Clinical Trial In macroVascular Events) which included patients with T2DM treated with pioglitazone in secondary prevention, demonstrated benefits of reducing events (myocardial infarction, stroke), but also increased risk for heart failure [61]. DPP-IV-inhibitors (dipeptidyl peptidase IV), are CV safe, body weight neutral, and with low risk for hypoglycemia. Insulin therapy is initiated at HbA1c values above 10%, or in the presence of symptoms of hyperglycemia. New generations of basal insulin analogues are

Mention: only the statistically significant results are included in the table; HR-hazard ratio; NS-non statistically significant; MACE-major adverse cardiovascular events: CV mortality, non-fatal myocardial infarction and non-fatal stroke; hHF- hospitalization for heart failure; Renal effects: new or worsening nephropathy (persistent macroalbuminuria, persistent doubling of the serum creatinine level and a creatinine clearance of less than 45 ml per minute per 1.73 m2 of body-surface area, or the need for continuous renal-replacement therapy); LEADER- Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drugnaïve Subjects With Type 2 Diabetes; EXSCEL- Exenatide Study of Cardiovascular Event Lowering Trial; EMPA-REG-OUTCOME-The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose; CANVAS- Canagliflozin Cardiovascular Assessment Study; DECLARE-

TIMI 58-Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in

has significantly reduced the primary composite outcome of death from

At a systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, drug therapy is necessary in combination with nonpharmacological treatment [12, 19]. An association of antihypertensive classes is often needed, with a renin-angiotensin-aldosterone system (RAAS) blocker, and a calcium channel blocker or diuretic. A RAAS blocker is recommended particularly in the presence of microalbuminuria, albuminuria, proteinuria, or LV hypertrophy. Dual therapy is recommended as first-line treatment, with a combination of a RAAS blocker with a calcium channel blocker or thiazide/thiazide-like diuretic. It is recommended that at least one antihypertensive drug to be administered

hospitalizations for heart failure (HR = 0.70) [64].

*5.3.2 Pharmacotherapy of hypertension*

cardiovascular causes or hospitalization for HF (HR = 0.75) and the total number of

Unfortunately, the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was unable to demonstrate that once-weekly exenatide can achieve a statistically significant reduction in the incidence of major adverse cardiovascular

DAPA-HF study ("Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure"), which included patients with heart failure (ejection fraction <40% and NYHA class II-IV or symptoms) has demonstrated, after a median of 18.2 months of treatment with dapagliflozin vs. placebo, a significant reduction (HR = 0.74) of the primary composite outcome (worsening heart failure or death from cardiovascular causes) and the secondary outcomes (cardiovascular death or heart-failure hospitalization) (HR = 0.75) [63]. A similar design has been used in EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction). Compare to placebo, empagliflozin

Myocardial Infarction 58.

events, compare to placebo [62].

**286**

LDL-cholesterol is the first therapeutic target. Depending on the risk class, statins are used in moderate doses (Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin 20–40 mg) or high doses (Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg) [12, 19, 48]. If LDL-C target is not reached, ezetimibe or PCSK9 inhibitors (evolocumab or alirocumab) are added. In the presence of atherogenic dyslipidemia (persistent triglycerides >200 mg/dl), the fenofibrate can be added to statin. The lipid arm of ACCORD study showed a further 31% reduction in CV events' relative risk in this combination. Omega-3 fatty acids can further reduce the level of triglycerides in a dose of >2 g/day. The "Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) study", showed that 2 grams icosapent ethyl (EPA), administered twice daily, was associated with 25% relative risk reduction (P < 0.001) in major adverse CV events (MACE), compared to placebo [65].
